Endotoxin enhances hypoxic constriction of rat aorta and pulmonary artery through induction of EDRF/NO synthase

P. Zelenkov, T. McLoughlin, R. A. Johns

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


The vascular response to hypoxia in endotoxin (lipopolysaccharide: LPS)- exposed rat pulmonary artery (PA) and thoracic aorta (AO) was investigated and the mechanism of the observed hypoxic responses defined. In isometric tension studies, LPS-treated AO and PA rings, with and without endothelium, demonstrated decreased (P < 0.05) contractile response to phenylephrine (PE EC50), and the dose response was shifted to the right (P < 0.01) compared with non-LPS treated rings. Both vessel types responded to hypoxia with a markedly increased (P < 0.01) and sustained (P < 0.01) constriction when preexposed to LPS. Control non-LPS rings with endothelium intact had a transient vasoconstriction in early hypoxia, which was abolished with removal of the endothelium. N(ω)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, increased the PE EC50 tension in LPS-treated rings, markedly reduced the duration and magnitude of the hypoxic vasoconstriction in LPS-treated rings, and attenuated the transient vasoconstriction seen in endothelium-intact, non-LPS rings (all P < 0.05). L- Arginine reversed the L-NAME effects. Hypoxia decreased guanosine 3',5'- cyclic monophosphate (cGMP) content 54 ± 4% in all LPS and 33 ± 4% in the non-LPS intact rings (P < 0.05). L-NAME reduced cGMP content 90 ± 5% in all LPS rings. Indomethacin inhibited formation of a constriction factor in aortic LPS-treated rings (P < 0.01) that was endothelium dependent and unaffected by the presence of L-NAME. These data confirm that the transient hypoxic constriction seen in non-LPS-treated vascular rings is due to hypoxic inhibition of constitutive NO synthase found in endothelium and demonstrate that the inhibition by hypoxia of LPS-induced NO synthase is the primary mechanism of the enhanced and sustained hypoxic vasoconstriction seen in LPS- treated vessels.

Original languageEnglish (US)
Pages (from-to)L346-L354
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number4 9-4
StatePublished - 1993
Externally publishedYes


  • N(ω)-nitro-L-arginine methyl ester
  • arachidonic acid
  • endothelium-derived relaxing factor
  • hypoxia
  • indomethacin
  • lipopolysaccharide
  • nitric oxide
  • nitric oxide synthase
  • sepsis
  • thoracic aorta
  • vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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